Calculation of PTAs

Calculates the Percent Target Attainment (PTA)

Usage

makePTA(
  simdata,
  simlabels,
  targets,
  target.type,
  success,
  outeq = 1,
  free.fraction = 1,
  start,
  end,
  icen = "median",
  block = 1
)

Arguments

simdata: Can be one of multiple inputs. Typically it is a vector of simulator output filenames, e.g. c("simout1.txt","simout2.txt"), with wildcard support, e.g. "simout*" or "simout?", or a list of PMsim objects made by simdata with suitable simulated regimens and observations. The number and times of simulated observations does not have to be the same in all objects. It can also be a PMpta object previously made with makePTA can be passed for recalculation with a new success value or simlabels. Finally, PMpost and PMmatrix objects are also allowed.
simlabels: Optional character vector of labels for each simulation. Default is c('Regimen 1', 'Regimen 2',...).
targets: A vector of pharmacodynamic targets, such as Minimum Inhibitory Concentrations (MICs), e.g. c(0.25, 0.5,1,2,4,8,16,32). This can also be a sampled distribution using makePTAtarget.
target.type: A numeric or character vector, length 1. If numeric, must correspond to an observation time common to all PMsim objects in simdata, rounded to the nearest hour. In this case, the target statistic will be the ratio of observation at time target.type to target. This enables testing of a specific timed concentration (e.g. one hour after a dose or C1) which may be called a peak, but is not actually the maximum drug concentration. Be sure that the time in the simulated data is used, e.g. 122 after a dose given at 120. Character values may be one of "time", "auc", "peak", or "min", for, respectively, percent time above target within the time range specified by start and end, ratio of area under the curve within the time range to target, ratio of peak concentration within the time range to target, or ratio of minimum concentration within the time range to target.
success: A single value specifying the success statistic, e.g. 0.4 for proportion time (end-start) above target, or 100 for peak:target.
outeq: An integer specifying the number of the simulated output equation to use. Default is 1.
free.fraction: Proportion of free, active drug. Default is 1, i.e. 100% free drug or 0% protein binding.
start: Specify the time to begin PTA calculations. Default is a vector with the first observation time for subjects in each element of simdata, e.g. dose regimen. If specified as a vector, values will be recycled as necessary.
end: Specify the time to end PTA calculations so that PTA is calculated from start to end. Default for end is the maximum observation time for subjects in each element of simdata, e.g. dose regimen. If specified as a vector, values will be recycled as necessary. Subjects with insufficient data (fewer than 5 simulated observations) for a specified interval will trigger a warning. Ideally then, the simulated datset should contain sufficient observations within the interval specified by start and end.
icen: Can be either "median" for the predictions based on medians of pred.type parameter value distributions, or "mean". Default is "median".
block: Which block to plot, where a new block is defined by dose resets (evid=4); default is 1.

Value

The output of makePTA is a list of class PMpta, which has 2 objects:

results A data frame with the following columns: simnum, id, target, pdi.
- simnum is the number of the simulation; id is the simulated profile number within each simulation;
- target is the specified target;
- pdi is the target pharmacodynamic index, e.g. time > target, auc:target, etc.
outcome A data frame summarizing the results with the following columns: simnum, target, prop.success, pdi.mean, and pdi.sd. If targets was specified via makePTAtarget to be a sampled distribution, then the target column will be missing from the outcome table.
- simnum and target are as for results.
- prop.success is the proportion with a pdi > success, as specified in
- pdi.mean and pdi.sd have the mean and standard deviation of the target pharmacodynamic index (e.g. proportion end-start above target, ratio of Cmax to target) for each simulation and target.

There are several attributes for this object that reflect the conditions used to create it. Access the values of these attributes with attr(x, which)

as detailed in base::attr().

simlabels Values for the simlabels
simTarg Values for the targets
success Value for success threshold
type Value for target.type

Details

makePTA will calculate the PTA for any number of simulations, targets and definitions of success. Simulations typically differ by dose, but may differ by other features such as children vs. adults. This function will also accept data from real subjects either in the form of a PMpost or a PMmatrix object. If a PMpta object is passed to the function as the simdata, the only other parameter required is success. If desired, a new set of simlabels can be specified; all other parameters will be ignored.

Author

Michael Neely and Jan Strojil

Examples

if (FALSE) {
pta1 <- simEx$pta(
simlabels <- c("600 mg daily", "1200 mg daily", "300 mg bid", "600 mg bid"),
targets = c(0.25, 0.5, 1, 2, 4, 8, 16, 32), target.type = "time",
success = 0.6, start = 120, end = 144
)
pta1$summary()
pta1$plot()
}